Pharmacokinetics of CAMPATH-1H in BMT patients

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Abstract
CAMPATH-1 (CD52) Abs are used in stem-cell transplantation for prevention of GvHD and rejection. The humanized Ab CAMPATH- 1H has recently replaced the rat Ab CAMPATH-1G. There was a concern whether it might have a longer half-life in vivo and, possibly, cause prolonged immunosuppression post-transplant. Serum samples were collected pre- and post-transplant from patients receiving CAMPATH-1H at 10 mg/day according to two protocols: (A) from Day –5 to Day +4 (total dose, 100 mg), (B) from Day –10 to Day –6 (total dose, 50 mg). The Ab concentrations were measured using an immunofluorescence assay. Lymphocytes were substantially depleted by the second day of treatment and were below 0.1 × 109/L by the day of transplant and for at least 1 month post-transplant. By Day 90 there was a greater recovery in Group B, to a median of 0.32 × 109/L compared with 0.25 × 109/L in Group A. By Day 180, both groups had recovered to approx 0.52 × 109/L. Serum concentrations of CAMPATH-1H on the day of transplant were well above the level necessary for opsonization of lymphocytes. The peak Ab concentration was 6.1 μg/mL in Group A and 2.5 μg/mL in Group B. CAMPATH-1H could be detected in Group A for 23 days post-transplant, significantly longer than in Group B (11 days). The terminal half-life in the two groups was similar (range 15–21 days) and contrasts with the half-life of < 1 day previously estimated for CAMPATH-1G. There were no cases of graft failure and the incidence of GvHD was similar in the two groups. The humanized Ab CAMPATH-1H appears to persist in the circulation for longer than the original rat Ab CAMPATH-1G. This might contribute to delayed lymphocyte recovery and prohibit the use of early donor-lymphocyte infusions. A short course of treatment given early pre-transplant is likely to be preferable to the extended course given both pre- and post-transplant.